Class II MHC (major histocompatibility complex) cellular proteins (αβ heterodimers) associate early during biosynthesis with a type II membrane polypeptide, the invariant chain (Ii), to form class II MHC/invariant chain complexes (αβIi). It has been reported that the invariant chain associates with class II MHC molecules via direct interaction of residues 81-104 of its lumenal domain, designated “class II associated invariant chain peptides (CLIP)” therefor with the antigen binding groove of class II MHC.
The invariant chain contains a signal in its cytoplasmic tail which delivers the class II MHC/invariant chain complexes to intracellular endocytic compartments, where the class II MHC molecules encounter and bind antigenic peptides. A prerequisite for antigenic peptide loading of class II MHC molecules is the proteolytic destruction of the invariant chain from the class II MHC/invariant chain complexes. Identification of the specific key protease responsible for this proteolysis has not previously been reported. Proteolysis of the invariant chain allows the antigenic peptides to bind to the class II MHC molecules to form class II MHC/antigenic peptide complexes.
The antigenic peptides in these complexes are then deposited on the cell surface for recognition by CD4+ T cells. These T cells are involved in the production of cytokines and thus help orchestrate an immune response, culminating in the appropriate production of antibodies. On occasion, CD4+ cells are activated inappropriately and are believed to contribute to the pathology of autoimmune disease.